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TOPICAL AEROSOLS
The following tests are applicable to topical aerosols containing drug,in suspension or solution,packaged under pressure,and released upon activation of an appropriate valve system.USP28
Delivery Rate and Delivered Amount
Perform these tests only on containers fitted with continuous valves.
Delivery Rate—
Select not fewer than four aerosol containers,shake,if the label includes this directive,remove the caps and covers,and actuate each valve for 2to 3seconds.Weigh each container accurately,and immerse in a constant-temperature bath until the internal pressure is equilibrated at a temperature of 25
as determined by constancy of internal pressure,as directed under the Pressure Testbelow.Remove the containers from the bath,remove excess moisture by blotting with a paper towel,shake,if the label includes this directive,actuate each valve for 5.0seconds (accurately timed by use of a stopwatch),and weigh each container again.Return the containers to the constant-temperature bath,and repeat the foregoing procedure three times for each container.Calculate the average Delivery Rate,in g per second,for each container.
as determined by constancy of internal pressure,as directed under the Pressure Testbelow.Remove the containers from the bath,remove excess moisture by blotting with a paper towel,shake,if the label includes this directive,actuate each valve for 5.0seconds (accurately timed by use of a stopwatch),and weigh each container again.Return the containers to the constant-temperature bath,and repeat the foregoing procedure three times for each container.Calculate the average Delivery Rate,in g per second,for each container.
Delivered Amount—
Return the containers to the constant-temperature bath,continuing to deliver 5second actuations to waste,until each container is exhausted.[NOTE—Ensure that sufficient time is allowed between each actuation to avoid significant canister cooling.]Calculate the total weight loss from each container.This is the Delivered Amount.
Pressure Test
Perform this test only on topical aerosols fitted with continuous valves.
Select not fewer than four aerosol containers,remove the caps and covers,and immerse in a constant-temperature bath until the internal pressure is constant at a temperature of 25.Remove the containers from the bath,shake,and remove the actuator and water,if any,from the valve stem.Place each container in an upright position,and determine the pressure in each container by placing a calibrated pressure gauge on the valve stem,holding firmly,and actuating the valve so that it is fully open.The gauge is of a calibration approximating the expected pressure and is fitted with an adapter appropriate for the particular valve stem dimensions.Read the pressure directly from the gauge.
.Remove the containers from the bath,shake,and remove the actuator and water,if any,from the valve stem.Place each container in an upright position,and determine the pressure in each container by placing a calibrated pressure gauge on the valve stem,holding firmly,and actuating the valve so that it is fully open.The gauge is of a calibration approximating the expected pressure and is fitted with an adapter appropriate for the particular valve stem dimensions.Read the pressure directly from the gauge.
Minimum Fill
Topical aerosols meet the requirements for aerosols under Minimum Fill á755ñ.
Leakage Test
Perform this test only on topical aerosols fitted with continuous valves.
Select 12aerosol containers,and record the date and time to the nearest half hour.Weigh each container to the nearest mg,and record the weight,in mg,of each as W1.Allow the containers to stand in an upright position at a temperature of 25.0±2.0for not less than 3days,and again weigh each container,recording the weight,in mg,of each as W2,and recording the date and time to the nearest half hour.Determine the time,T,in hours,during which the containers were under test.Calculate the leakage rate,in mg per year,of each container taken by the formula:
for not less than 3days,and again weigh each container,recording the weight,in mg,of each as W2,and recording the date and time to the nearest half hour.Determine the time,T,in hours,during which the containers were under test.Calculate the leakage rate,in mg per year,of each container taken by the formula:(365)(24/T)(W1-W2).
Where plastic-coated glass aerosol containers are tested,dry the containers in a desiccator for 12to 18hours,and allow them to stand in a constant-humidity environment for 24hours prior to determining the initial weight as indicated above.Conduct the test under the same constant-humidity conditions.Empty the contents of each container tested by employing any safe technique (e.g.,chill to reduce the internal pressure,remove the valve,and pour).Remove any residual contents by rinsing with suitable solvents,then rinse with a few portions of methanol.Retain as a unit the container,the valve,and all associated parts,and heat them at 100for 5minutes.Cool,weigh,record the weight as W3,and determine the net fill weight (W1-W3)for each container tested.[NOTE—If the average net fill weight has been determined previously,that value may be used in place of the value (W1-W3)above.]The requirements are met if the average leakage rate per year for the 12containers is not more than 3.5%of the net fill weight,and none of the containers leaks more than 5.0%of the net fill weight per year.If 1container leaks more than 5.0%per year,and if none of the containers leaks more than 7.0%per year,determine the leakage rate of an additional 24containers as directed herein.Not more than 2of the 36containers leak more than 5.0%of the net fill weight per year,and none of the 36containers leaks more than 7.0%of the net fill weight per year.Where the net fill weight is less than 15g and the label bears an expiration date,the requirements are met if the average leakage rate of the 12containers is not more than 525mg per year and none of the containers leaks more than 750mg per year.If 1container leaks more than 750mg per year,but not more than 1.1g per year,determine the leakage rate of an additional 24containers as directed herein.Not more than 2of the 36containers leak more than 750mg per year,and none of the 36containers leaks more than 1.1g per year.This test is in addition to the customary in-line leak testing of each container.
for 5minutes.Cool,weigh,record the weight as W3,and determine the net fill weight (W1-W3)for each container tested.[NOTE—If the average net fill weight has been determined previously,that value may be used in place of the value (W1-W3)above.]The requirements are met if the average leakage rate per year for the 12containers is not more than 3.5%of the net fill weight,and none of the containers leaks more than 5.0%of the net fill weight per year.If 1container leaks more than 5.0%per year,and if none of the containers leaks more than 7.0%per year,determine the leakage rate of an additional 24containers as directed herein.Not more than 2of the 36containers leak more than 5.0%of the net fill weight per year,and none of the 36containers leaks more than 7.0%of the net fill weight per year.Where the net fill weight is less than 15g and the label bears an expiration date,the requirements are met if the average leakage rate of the 12containers is not more than 525mg per year and none of the containers leaks more than 750mg per year.If 1container leaks more than 750mg per year,but not more than 1.1g per year,determine the leakage rate of an additional 24containers as directed herein.Not more than 2of the 36containers leak more than 750mg per year,and none of the 36containers leaks more than 1.1g per year.This test is in addition to the customary in-line leak testing of each container.
Total Number of Discharges per Container
Perform this test only on topical aerosols fitted with dose-metering valves,at the same time as,and on the same containers used for,the test for Uniformity of Dosage Units á905ñ.Determine the total number of discharges or deliveries by counting the number of priming discharges plus those used in determining the spray contents,and continue to fire or discharge until the container or inhaler is empty.The requirements are met if all the containers or inhalers tested contain not less than the number of discharges stated on the label.
Delivered-Dose Uniformity
The test for Delivered-Dose Uniformity is required for topical aerosols fitted with dose-metering valves.For collection of the minimum dose,proceed as directed in the test for Delivered-Dose Uniformityunder Metered-Dose Inhalers and Dry Powder Inhalers,as described below,except to modify the dose sampling apparatus so that it is capable of quantitatively capturing the delivered dose from the preparation being tested.Unless otherwise stated in the individual monograph,apply the acceptance criteria for Metered-Dose Inhalers and Dry Powder Inhalersas described below.